Study Evaluating Subjects With Distal Renal Tubular Acidosis

• ClinicalTrials.gov Identifier: NCT03644706
• Recruitment Status: Recruiting
• First Posted: August 23, 2018
• Last Update Posted: September 6, 2019
• Sponsor: Advicenne Pharma
• Information provided by (Responsible Party): Advicenne Pharma

Study Description

Brief Summary:

This is a phase 3, prospective, multicenter, randomized, double-blinded, placebo-controlled, study product withdrawal study comparing the efficacy of ADV7103 versus placebo in preventing the development of metabolic acidosis defined by serum bicarbonate level in pediatric (6 months to < 18 years of age) and adult (18 to 65 years of age) subjects with primary dRTA.

Condition or disease	Intervention/treatment	Phase
Distal Renal Tubular Acidosis	Drug: ADV7103; Drug: Placebos	Phase 3

Detailed Description:

The study will target enrolling at least 4 subjects in each of the following age groups: 6 months - 23 months; 2-11 years, and ≥ 12 years. Subjects will be in the study for up to 21 weeks. After screening and enrollment, subjects will participate in an 8-12 week open label period where there dose of ADV7103 will be titrated to effect, then continued for the remainder of the open label period. Periodic measurements of bicarbonate and potassium levels will be collected during this period. Following the open-label period, subjects will enter a 6-day randomized withdrawal period. For this portion of the study, subjects will be admitted to an inpatient setting. A follow-up period up to four weeks on re-established therapy completes the trial. Subjects will have the opportunity to subsequently enter a long-term, open label extension.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 3 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Withdrawal Study Evaluating ADV7103 In Pediatric and Adult Subjects With Distal Renal Tubular Acidosis (dRTA)
• Actual Study Start Date: January 31, 2019
• Estimated Primary Completion Date: February 1, 2021
• Estimated Study Completion Date: February 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ADV7103; Patients continue to receive ADV7103 twice a day at their open label dose over 6 days	Drug: ADV7103; Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances. The strength is 6.44 (± 10 %) mEq/g of ADV7103 (alkalinizing power).; Other Name: Potassium Citrate and Potassium Bicarbonate
Placebo Comparator: Placebo Comparator; Patients receive matched placebo twice a day until they reach a bicarbonate level of 18mEq/L	Drug: Placebos; Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules. Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.

Outcome Measures

Primary Outcome Measures :

1. Mean change in blood bicarbonate levels [ Time Frame: 6 days ]
   Compare the efficacy of ADV7103 versus placebo in preventing metabolic acidosis, defined as 2 consecutive serum bicarbonate levels < 18 mEq/L for subjects ≥ 4 years old and < 17 mEq/L for subjects < 4 years old, during the Withdrawal Period

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female or male subjects ≥ 6 months of age and ≤ 65 years of age at time of consent;
2. Subject presents with a previous diagnosis of primary dRTA of at least 4 months duration for subjects < 12 years of age, and at least one year for those ≥ 12 years of age, based on documented history of non-anion gap, hyperchloremic, hypokalemic metabolic acidosis;
3. Subject requires ≥ 0.9 mEq/kg/day of alkali therapy to maintain serum bicarbonate levels above the LLN for the laboratory providing results;

Exclusion Criteria:

1. Female subject who is pregnant or lactating or has plans for pregnancy during the study;
2. Subject has evidence of proximal tubule dysfunction (eg, hypophosphatemia, low serum uric acid, glycosuria, or amino aciduria);
3. Subject presents with another diagnosed condition as a potential etiology for her/his dRTA (eg, systemic lupus erythematosus, Sjogren's syndrome), in the opinion of the Investigator;
4. Subject requires therapy with potassium sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, trimethoprim, drospirenone and other progestins, nephrotoxic antibiotics, penicillins, tacrolimus, or medications known to delay gastric emptying or otherwise interfere with absorption of study product;
5. Subject has evidence of obstructive uropathy or other findings on renal ultrasound associated with Visit 1 expected to require intervention during the course of the study, in the opinion of the Investigator;

6. Subject has any of the following laboratory abnormalities associated with Visit 1:

   1. AST and/or ALT > 1.5x upper limit of normal (ULN)
   2. Serum potassium > 5.0 mEq/L or hypokalemia accompanied by clinical symptoms (eg, muscle cramps) or significant ECG changes (eg T wave depression, U wave elevation)
   3. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (according to the updated Schwartz formula for children and Chronic Kidney Disease - Epidemiology Collaboration [CKD-EPI] formula for adults)
   4. Total bilirubin > ULN, except with known Gilbert's disease.
7. Subject has been hospitalized or had outpatient surgery (other than minor skin and dRTA disease-related procedures or ear tube placement) in the past 6 months or is planning surgery in the next 6 months;

Contacts and Locations

Locations

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Kathleen Peoples 720-777-4708 Kathleen.peoples@childrenscolorado.org

Principal Investigator: Bradley Dixon, MD

United States, Connecticut

Connecticut Children's; Recruiting

Hartford, Connecticut, United States, 06106

Contact: Krystal Perez 860-837-6359 KPerez02@connecticutchildrens.org

Principal Investigator: Cynthia Silva, MD

United States, Florida

University of South Florida Pediatric Infectious Disease; Recruiting

Tampa, Florida, United States, 33606

Contact: Denise Casey, RN 813-259-8674 dcasey1@health.usf.edu

Principal Investigator: Valerie Panzarino, MD

United States, Georgia

Emory Children's Center; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Christy Kang 404-712-9998 christy.kang@emory.edu

Principal Investigator: Laurence Greenbaum, MD

United States, Indiana

J.W. Riley Hospital for Children; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Sherry Wilson 317-274-2576 slw2@iu.edu

Principal Investigator: Amy Wilson, MD

United States, Missouri

Washington University/St. Louis Children's Hospital; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Leslie Walther 314-747-1349 leslie.walther@wustl.edu

Principal Investigator: Kevin Barton, MD

United States, New York

Montefiore Medical Center; Recruiting

Bronx, New York, United States, 10467

Contact: Patricia Flynn, RN 718-655-1120 PFLYNN@montefiore.org

Principal Investigator: Kimberly Reidy, MD

Canada, Alberta

University of Alberta; Recruiting

Edmonton, Alberta, Canada, T6G 2R3

Contact: Dory Sample 780-248-5599 Dory.Sample@albertahealthservices.ca

Principal Investigator: R. Todd Alexander, MD

Canada, Ontario

The Hospital for Sick Children; Not yet recruiting

Toronto, Ontario, Canada, M5G 1X8

Contact: Natasha Jawa 416-813-7654 natasha.jawa@sickkids.ca

Principal Investigator: Damien Noone, MD

Sponsors and Collaborators

Advicenne Pharma

Investigators

• Study Director: Linda Law, MD; Advicenne Pharma

More Information

Additional Information:

Patient information regarding the disease under study and protocol information  Patient education  Company website 

• Responsible Party: Advicenne Pharma
• ClinicalTrials.gov Identifier: NCT03644706 History of Changes
• Other Study ID Numbers: B23CS
• First Posted: August 23, 2018
• Last Update Posted: September 6, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acidosis, Renal Tubular; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Potassium Citrate; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Expectorants; Respiratory System Agents